• njikomes

Andrew Chadeayne: Chemistry of Magic Mushrooms, DMT Analogues, Entourage Effects in Cannabis & Fungi

Full episode transcript below. Beware of typos!

Nick Jikomes

All right, Andrew Chadeayne. Thank you for joining me.

Andrew Chadeayne 4:39

Thank you for having me.

Nick Jikomes 4:40

Can you start off by just telling everyone a little bit about who you are and what your scientific background is before going into CaaMTech?

Andrew Chadeayne 4:47

Sure. I'm interested in and I started studying science at Princeton University. I started out studying neuro psychology, addiction and reward in the Partly herbal lab. And I was looking at models for addiction and the paper that came out of that was showing that sugar is addictive through some of the same pathways as opiate drugs, even as an undergrad that led me to a fascination with the underlying chemicals and molecules. And so I'd actually graduated with a degree in chemistry from Princeton, and then went on to do a PhD at Cornell, in chemistry. That work was very academic, not a lot of real world applications. But I spent five years learning how to leave absolutely no stone unturned with Peter rolls and ski at Cornell. And, at the end of that time, for better or worse, my plans to become a chemistry professor sort of disappeared, because I didn't think that I was possibly smart enough to be a chemistry professor working for this super brilliant chemist, peoples and ski. And so I looked for some other area where I might, you know, find a better fit. I started taking classes at Cornell Law School, and ultimately decided to make a transition into patent law. So after getting my PhD, I moved to Cambridge, Massachusetts, and started working for a patent firm called Finnegan as a technical specialist, advising on chemical matters, and immediately realized that now I was a smart chemist, because to take the chemical skill set and move it over into the legal profession. Now I've got like a superpower, especially coming from a group that focuses on you know, really digging down deep and leaving no stone unturned. So I stayed with Finnegan for five years, and went to law school at GW law school in Washington, DC. And after I was done with law school, I made another move into more entrepreneurial waters and started a company called swim spray, which gets the chlorine off of hair and skin, it is the absolute best solution for getting chlorine off of you after you swim. But it turns out that there was not a tremendous market for telling swimmers that they smelled like chlorine and needed to get the chlorine off their hair and skin. From there. Since you know swim spray wasn't paying the bills at the time. And I had some interest from some of my clients and people that knew I did patent law. I went into private practice, patent law, started a patent firm, which I ran for about five years. And it was through that patent firm that I connected with a company called Abu Abu was a cannabis company that was doing really innovative work that really captured my interest in a variety of different ways. One, looking at the chemical composition of cannabis and not just calling it weed. And then two, I had a long standing curiosity with the patentability of new forms of natural products, new combinations that were possible after looking at the chemical composition. So after a while of you know, being a booze, Patent Agent or patent attorney, while running my patent firm, I made the transition over to Edwin full time as their director of innovation. Then eventually Eboo got bought by Canopy Growth. And I was left looking for the next thing. And fortunately, at that time, you know, living in the Pacific Northwest, magic mushrooms grow in my backyard. I sort of started asking myself whether, you know, there are other sort of underappreciated molecules and chemicals or, you know, other natural sources that are sort of treated like one molecule that really have a lot more going on in them when you look closer. So I decided to look more closely at magic mushrooms. And that was probably 2016 2017. And I've been working on that and all sorts of other questions and roads that have opened up because of that,

Nick Jikomes 8:49

did it? Did it really just sort of occur to you to think about magic mushrooms in that kind of spontaneous way you just described? Or had you been? Had they been on your mind longer than that?

Andrew Chadeayne 8:59

I think it was a combination of things. One the, you know, the PhD experience of you know, no, absolutely everything that's going on chemically all the time. Don't ignore anything that matters. Plus, how I had just come off of several years working in cannabis. And one of the things that was coming out in cannabis at the time was that it's not just THC, there's these other molecules, and we were really at the forefront of looking at that. And so those two things kind of came together with magic mushrooms and led me to ask, well, is that just psilocybin? And if it's not just psilocybin could maybe some of those other molecules matter? Yeah.

Nick Jikomes 9:36

Let's actually talk about some cannabis stuff. First, to segue into what you're doing now. And one of the concepts I want to talk about with you in particular, is this idea of an entourage effect are different entourage effects. So can you break that down for people with respect to cannabis? What do we mean when we start talking about entourage effects?

Andrew Chadeayne 9:56

Oh, boy. I'll now be another person pretending to know I think at a high level, everybody understands what it means it means that, you know, the some of the chemicals that are that are in the plant or in the formulation that are consumed by the user work together to produce an effect that is distinct from what you would get from an individual molecule, or even by what you would guess you would get by looking at the different individual molecules. And that they work to kick together in this entourage, or I've heard other people call it a symphony, you know, to create an effect that's bigger than the sum of the parts.

Nick Jikomes 10:32

And is this just like, a cool idea? Or is there any kind of precedent for this anywhere in nature?

Andrew Chadeayne 10:39

I think it's both it's, it's it's the in between, that's gray. And that's what's so fun about it for me is that, you know, you're you're chasing after something. And you know, it's there. But you can't, it's the connecting of the dots. That's the challenge. And so we, you know, I'm 100% convinced that there is a, quote, entourage effect, I think anyone will tell you that, you know, the different strains of cannabis result in a different experience when consumed by the user. We've also shown this using cellular pharmacology, assays and whatnot. In the magic mushrooms space, which is where I've been focusing recently, there are some pretty conclusive studies showing that mushroom extracts have an effect that is different from psilocybin. And so you know, there's a difference. But predicting it and harnessing it and using it in a way to get what you want. That's I think that's going to be a long term challenge.

Nick Jikomes 11:34

Yeah, that's always been my intuitive, a very strong intuition. And the way that I've always explained it on the cannabis side to people, which is that entourage effects are almost certainly real to some extent, it's just that no one has sort of parsed what the specific ones are. And no one's sort of, like, decoded what that chemical language is. But there's many examples in nature, where plants and other creatures are using chemistry combinatorial effects with chemistry to achieve things that aren't achievable, or not as achievable as any of the single molecules on their own. So we sort of know this stuff is out there, we just haven't like fully, fully decoded it.

Andrew Chadeayne 12:12

Yes. And I mean, I think it's a big project, nature tends to be very sophisticated, and very, very good at putting together these sorts of cocktails. The example that I use a lot is that I can't wake up in the morning and not have my cup of coffee. I mean, my my five year old has learned how to bring data a cup of coffee before it's okay to you know, get the morning routine going. But, you know, when there's no coffee in the house, I'm not looking for a caffeine pill. And I would I would bet that the effects of coffee, you know, in some quantifiable way are different from caffeine, that probably the, you know, terpenes or fight halls or what have you in the coffee, other molecules modulate the effects that you know, quantifiably would cause you a different experience with those molecules visa vie a caffeine pill.

Nick Jikomes 13:03

So in cannabis, I would say, you know, the one clear example of an interactive effect between two or more compounds is THC and CBD. We know that THC is the main psychoactive component of cannabis. It has been known known to be that for a long time, it activates the CB one receptor to have most of its effects CBD interacts with that same receptor but in a different way. And so there's there's sort of a known mechanistic basis for why the THC CBD ratio would be really important for mediating some kind of entourage like effect. And we know from various studies that you know, having CBD in combination with THC can mitigate some of the negative side effects of THC for example, the other thing that that's sort of a hot topic these days is the idea that terpenes the the aromatic compounds, also found in cannabis and other plants might modulate the effects of THC based on your background and what's been done. Some of its maybe in the published literature, some of its maybe not in the published literature. Is there any clear evidence in your mind out there that the terpenes are likely causing there are specific entourage effects involving THC in any of the cannabis terpenes

Andrew Chadeayne 14:14

I can say for sure that there is and we can come at it a bunch of different ways. For one I think it's pretty well figured out that no one likes pure THC like I think and there was a it was Marinol maybe. And there have been products made, you know, both in the pharmaceutical and the recreational market, you know, that are pure THC get rid all that other stuff. Do Western medicine, just THC and nobody likes it. And I think the principal side effect there is anxiety, paranoia. And so, that right there tells you there's an entourage effect because people do sort of like smoking weed. And when you formulate the THC with other molecules into your gummies or mints or whatever it is those formulations people really like those So getting back to THC and CBD, yes, CBD reacts at the same receptor, the CB one receptor that THC does. And it modulates the way that THC behaves at that receptor. connecting that to a better user experience is a little bit more difficult. But now we've just basically proved the entourage effect, right? We know at a cellular level, that when CBD is in the mix, THC is actually less potent at that receptor, but it turns into a full agonist. So you, you get less of a response for, you know, a certain amount, but you can get higher, higher up in the in the response curve.

Nick Jikomes 15:38

So on its own THC is what we call a partial agonist and you're saying in the presence of CBD, it's actually a full agonist.

Andrew Chadeayne 15:45

I think it's a full agonist, or at least it tends towards a full agonist with with CBD in the mix. And that's that allosteric modulation at the CD, one receptor.

Nick Jikomes 15:53

I see. And so you think that's likely to be true for some of the terpenes as well, something like that. I

Andrew Chadeayne 15:57

happen to know that it's true with cannabis terpenes and cannabis ligands. I don't have the data in front of me. And it's been a while since I was in the cannabis industry. But we did. quantifiably using cellular assays show that cannabis ligand plus terpene equals different responses. And in many cases, you know, I can remember that the potency would go up, you know, four to 10 fold. Wow, big.

Nick Jikomes 16:20

Wow. So that does that is at least consistent with the intuition that many cannabis consumers have, which is that there's some kind of difference in potency, which doesn't appear to be completely explained by difference in the absolute levels of THC present.

Andrew Chadeayne 16:34

Yes, absolutely. I mean, if it were just THC, everything would be the same, right. And there seems to be a pretty big difference all the way from I don't like this. And it makes me anxious to wow, this really calms my nerves.

Nick Jikomes 16:45

Interesting. So you sort of have this interesting trajectory, from chemistry to law, working in the cannabis space, mentioning that mushrooms were growing in your backyard? Do you know what species are actually literally growing in your backyard? Philosophy, sign essence. Okay, so those are super potent ones Correct?

Andrew Chadeayne 17:02

Rumor has it? I think the data says that, you know what I mean, that that's actually the problem with all magic mushrooms, right? Is that, you know, huge variability. Right? So I mean, for any given species is that species more potent than another one, like, maybe on average, but for a given mushroom or parts of the mushroom, you can be, you know, a tenfold difference one way or another. It is called the potent philosophy. So I think that tells you something there. But I mean, in terms of, I think, you know, what everybody would point to is the most potent, I think it's still the philosophy as a residence, which is another Pacific Northwest.

Nick Jikomes 17:37

Yeah, there's definitely a lot of a lot of mushrooms out here. So why don't we get into camp tech? How did you? How did you get into cam tech? And can you just talk about what what cam tech is and why you started? Sure.

Andrew Chadeayne 17:51

I mean, it just really gets to and you pointed out, you know, I kind of jumped around in my career a lot, you know, my wife has always encouraged me to just do what I like doing, you know, that the results will kind of come. And so that was largely Eboo. You know, it was in patent law, and like, you know, what would be my dream client and chemical patent law, like, oh, it'd be fun to go and mess around with this sort of growing industry over here. And yeah, so when, you know, when my role at Abu and in cannabis sort of came to an end, there, I had this other fascinating little, little organism growing there in my yard. So I mean, like, the proximity to it, that was definitely part of it, that I could see these things growing in the fall. Also, super interesting class of molecules, no one really understood them, you know, they had been sort of, you know, pushed out of scientific research for quite some time. But, you know, in 2016 2017, there was just a little hint that these could be really important, you know, as medicines, you know, for treating, you know, some conditions, I think, at the time, you know, depression, anxiety and addiction had been hinted at, or shown, at least in some models. And then the chemist and me was, you know, geez, could this possibly be kind of the same thing that I've seen in cannabis? You know, are there other molecules in there? And what did they do and, you know, searched the Internet a little bit, and people will tell you that they're, Oh, these are more visual. And these are more body and it just sort of started feeling like cannabis again, which felt like another another puzzle, and another one that people hadn't started playing with yet, so I could play with it all by myself for a while.

Nick Jikomes 19:27

Yeah. So how did you actually go about starting a company around that?

Andrew Chadeayne 19:33

Well, I just exited Abu. So I plenty of money. Didn't need to work anymore. And running a company, by yourself tends not to be terribly expensive. Yeah, I spent a lot of time sitting in my garage office, reading all the papers that I could, you know, coming up with some hypotheses for what some of these molecules ought to be, which is a good starting point. If you're going to start looking at the chemo types of the of the mushrooms you at least want to kind of know what you're looking for like Um, mass number, or, you know, some other characteristics of those molecules that could be identified by by spectroscopy. You know, so, you know, a lot of sort of paper chemistry for the first year, I also learned about mushrooms and mushroom cultivation and the different, you know, substrates and the different processes and growing mushrooms. I took Paul Stamets, his mushroom cultivation seminar, you know, read all the books I could on magic mushrooms and other psychedelics and what receptors and serotonin. And, you know, started coming up with and I guess this is how I tend to do things started coming up with questions. Yeah. You know, one that I remember dawning on me was, you know, if you look at the absolute chemical composition of mushroom substrates, and compost and grain and whatnot, you know, the first thing that kind of dawned on me was, how do we mass balance this, you know, like, what is my yield of mushrooms going to be? You know, because how many nitrogen atoms do I have? Because, you know, if you look at all the sort of composting and mushroom growing books, like it doesn't quite add up, how you could, you know, you know, and those sorts of things bother me because there's no way around conservation of mass in my world. And so I mean, that was, you know, one example of one question, the other obviously being, what are the other molecules in there? And, you know, what, what did they do? The bluing reaction? Yeah, was another one that at the time really fascinated me, and I started messing around with that. And that, can you describe what that is for people? Sure. When many species of magic mushrooms get bruised or bumped into or cut, they tend to blue in color. And it's a noticeable sort of blue indigo color. separate topic, there are different shades of blue, and sometimes it's green, and why is that you can see how it morphs into other questions. But what is that blue stuff? That was kind of the question at the time. And so that's actually led to some really fruitful collaborations, in particular with Dirk Hofmeister, who I think, would probably be the world's expert in the bluing reaction now. And it turns out that the bluing reaction is actually due to oxidation of these psychedelic molecules. And through the oxidation they can connect themselves are coupled together into dimers and ligaments, and it's those diamonds and ligaments that, give it the blue color. And then I think kind of the funny punchline to that is, and, you know, this is, you know, all the credit goes to Dirk Hofmeister here, you know, maybe these mushrooms aren't making, you know, these tryptamines or psilocybin to get people high. Maybe they're making them so that when they get damaged, they can quickly put them together into one of these dimers that then can bind to protein or cause some sort of reaction as a defense mechanism.

Nick Jikomes 22:48

I see. That's interesting. I did want to ask you, like, you know, ecologically, why would an organism make something that happens to be psychoactive in a mammalian context? You know, one hypothesis is, they actually want evolutionarily speaking to be psychoactive, but another that you just hinted at, is that they're doing something else with it. You talked about defense, which seems to be a theme in the plant world, when you think about these molecules, whether it's cannabis, or philosophy mushrooms, so can you can you unpack that a little bit more about why the mushroom would even want to make these molecules so to speak?

Andrew Chadeayne 23:20

Sure, sure, the place I always have to remind myself to start here is that the mushrooms don't care about you, they could care less about your personal experience, or your your mystical experience or anything like that. They're they're off there being mushrooms. So to think that the mushrooms are making these molecules for me, I think is a very well, that's a very popular human view, that they must be doing it for me. The the defense mechanism tends to fit a lot better, I think, because you know, these mushrooms want to stay alive so that they can, you know, pass on their genes and continue to grow in their environment. And so looking for, like, those sorts of defensive mechanisms, I think makes more sense when asking why the mushrooms are doing it. And they're, you know, it's kind of hard to find a reason why the mushroom would make psilocybin I mean, in people. Sure, there's a pretty intense experience that the person goes through, but there's really no toxicology problems with that. So that can't be the answer there. And I think the same with, you know, at least other mammals. So I mean, there, you really can't come up with a good reason why the mushroom would make psilocybin or Bay asst or anything like that. But in terms of these dimers, one of the hypotheses that we're investigating is that the dimers, you know, might be paralytics, or might have some toxicity, we know that they bind to proteins, the dimers do the blue dimers. So all of that fits, and it would make quite a bit of sense because when would the mushroom want to sort of launch this defense mechanism? Well, when something's eating it or damaging it, and when does this start happening? Oh, well, the mushroom tissue good damaged, and through the damage, now the molecules can get oxidized. And then as they get oxidized, they become susceptible to the dimerization reaction, which makes these blue dimers and oligomers. And so it's sort of like an on demand defense system for them.

Nick Jikomes 25:14

I see when you say dimerized and oligomerize, you just mean individual molecules literally starting to link up and creating larger structures.

Andrew Chadeayne 25:21

Exactly that dimers to a ligament is more than too

Nick Jikomes 25:25

interesting. So it could literally be some kind of physical defense barrier thing.

Andrew Chadeayne 25:30

Yes. And then it makes a lot more sense than the mushrooms caring about my mental health.

Nick Jikomes 25:36

Interesting. So getting into some of the chemistry now, Can you unpack for people like what is psilocybin as a chemical structure, and how is it's actually synthesized within the biochemical pathways of these mushrooms.

Andrew Chadeayne 25:52

Let me see if I can do that off the top of my head. So psilocybin is a pretty simple molecule, it's a tryptamine molecule, which means that you know, it's a it's two rings fused to one another very similar to tryptophan, which we have in our bodies, which I believe is the first part of the biosynthesis in that tryptophan gets decarboxylated or loses its carboxylic acid group to make tryptamine, then the tryptamine has another oxygen atom added. So making psilocybin would be added in the four position of the tryptamine. And then that part of the molecule gets a phosphate group put on and it gets phosphorylated. And then the ethanolamine part of the molecule gets a first methyl group put on it and that's how we make base system before we put the methyl group on it, it would be nor Bay asst that one methyl group is Bay, Asst, then it gets mess methylated again, and you get psilocybin, there is another molecule after that called a Rogosin, which has a third methyl group on it. But it is unclear right now how that third methyl group gets on there.

Nick Jikomes 26:57

So I'm seeing an analogy here with cannabis where you've got these sort of biochemical pathways where one molecule gets turned into another one. And so depending on the growth characteristics, or the level of maturation, that the plant or in this case, the mushrooms at when you harvest it and process it, it's going to dictate to some extent the ratio of some of these different compounds how how far on the pathway, you've gone. And so they're they're all sort of like one or two steps from each other. Right? They are

Andrew Chadeayne 27:24

all definitely still one or two steps from one another. And it makes perfect sense, when you look at a scheme, you know that you know, compound, one goes to two to three to four to five, and they actually kind of the the phosphorylated ones bassist and inorbit, Asst. Psilocybin and solution, or Rogosin, and four hydroxy, trimethyl. Tripped ammonium, those actually convert back and forth into one another. But as simple as that scheme is this idea of oh, well, we can just pick them earlier and get a different ratio, that still needs to get worked out. And it's quite possible that different species of magic mushrooms have different forms or amounts of enzymes, that cause each one of these little steps to go a little bit faster or a little bit slower, or if they're in equilibrium tends to shift the equilibrium a little bit one way or another. And so I think those things, if one of those things complicates the situation, like imagine six or seven of them all complicating it at the same time, and so how to get, you know, one molecule out of it is a hard question.

Nick Jikomes 28:25

Right? And so what are so you mentioned some of these other compounds? Can you what, what is known about things like biosystem, and some of these other molecules? Do we know? I mean, beyond the the raw chemistry, do we know if they have psychoactive effects, or interact with interesting receptors that might be of interest therapeutically?

Andrew Chadeayne 28:44

First answer is we know very, very little. And then frankly, like no one was looking at these in 2016 2017, which is why this became a great garage project for me. Since then, there's been a ton of great work done, and we're, you know, gaining ground quickly. But if you think about sort of the, you know, obvious set of molecules that you would expect to be in the magic mushrooms, you would have, you know, 012, or three methyl groups up on the ethanolamine arm, and then it could be phosphorylated or not phosphorylated. So now you have a set of eight, and those eight would be NorthBay asst, and four hydroxy tryptamine that has no methyls on there, then you would have Bay, Asst and North callosum, and then you would have psilocybin and solution, and then you would have a Rogosin and four hydroxy trimethyl trip demonium to fill out the set of eight. At the time, people knew about psilocybin and psilocin and had studied its cellular pharmacology and you know, 2016 2017 you know, folks at Johns Hopkins had done a lot of nice work and compass pathways was moving towards clinical trials, the other molecules, almost nothing, you know, but since then, Some folks have synthesized Bay asst and Rogosin. Alex Sherwood at the Sona Institute had a nice paper I think it was 2017 Maybe 2018 With those syntheses and you know Bay asst has at least shown some really interesting results. So Bay asst is a pro drug of nor solution. So just like psilocybin isn't the active molecule and magic mushrooms it hydrolyzes into solution. They assistant does the same thing with nor solution. So the the active component is this hydrolyzed molecule that's liberated by the pro drug when you consume it. And so if you look at the cellular pharmacology of norsu, lowson, it's arguably more potent in functional assays that the serotonin to a receptor than solution is,

Nick Jikomes 30:52

I see. So meaning you when you say functional assay, you mean doing experiments to measure its receptor interaction directly?

Andrew Chadeayne 30:58

Yes. So in vitro, you can do a binding affinity study, you know, how well does this ligand compete with a radio ligand? How well does it bind to the receptor, or a functional assay is looking at fluorescence to see how well that ligand makes the neuron fire. And they both have their advantages and disadvantages. But in any case, norsu lowson, binds really well with the serotonin to a receptor and in both binding affinity studies, and also, it was functionally very potent at the serotonin to a receptor. So you know, just taking that data there, you would expect, hey, we have another super potent solution like psychedelic and the mushrooms. But the rub there is that when you do another test, the head Twitch experiments, which is the gold standard for is this a trippy molecule, the mice don't shake their heads,

Nick Jikomes 31:53

I see. And so the head twitches, basically you give you give a known, you give a molecule known psychedelic effects in a human to a mouse. And because the mouse can't tell you if it's tripping, and it's kind of hard to discern, what people have discovered is that they kind of have this head Twitch response where they very quickly Twitch their head. And that's our proxy for whether or not something might be hallucinogenic and a human being.

Andrew Chadeayne 32:15

Yes, that is the state of the art, you give it to a mouse. And if the mouse twitches its head, there is a very strong correlation between a mouse touching its head and a person having a psychedelic experience

Nick Jikomes 32:25

is and how, how strong is that correlation? Are there any instances where we know something is hallucinogenic, but it doesn't do the head twitch or they do the head Twitch but we know that it's not hallucinogenic in humans?

Andrew Chadeayne 32:36

I think there are a couple of counter examples. But I mean, that still makes it just an unbelievably great assay. I think I'm gonna get this wrong. I think it might be lice, ceramide, so like, it's one of the relatives of LSD is a potent serotonin to a agonist. But when you give it to a mouse, no head Twitch response. And then I'm not sure if there's any anecdotal evidence about people eating it.

Nick Jikomes 32:58

And so this molecule that you've described, nor SCI lowson, is this. So it's apparently potentially more potent than psilocybin, it's activating serotonin to a receptors, the so called psychedelic receptor is this is this molecule tending to be in very minut quantities in the mushrooms, or there's some species that actually have a good amount of it.

Andrew Chadeayne 33:19

Both. For one, and in some mushrooms, it's, you know, barely there. So I mean, it's definitely a minor tryptamine. I think in other samples and other sets of mushrooms, that can be up to a third of the tryptamines that are present, which is a very appreciable amount. And if you look at, you know, some data for philosophy as essence mushrooms, you know, where it's present as about a third, a quarter or a third of the tryptamines, there, the absolute amount is considerable. Because remember, that's a mushroom that has a lot of these tryptamines. And so, you know, a third of a lot is more than you would get in a less potent mushroom. Yeah.

Nick Jikomes 33:58

So as a residence, that's the one that's anecdotally reported to be one of the trippiest species out there. And so there seems to be something that is potentially lining up here.

Andrew Chadeayne 34:09

Yeah, that'd be another. Another piece of very anecdotal evidence that I would put into the, I guess, entourage effect bucket. The other thing about bassist in North Wilson and the not chirpiness is that there is actually report of somebody taking pure bait asst and it's not just somebody, it's Paul Stamets who, normally I would dismiss, you know, an N equals one self administered study where someone's eating drugs. But this is Paul Stamets. He knows magic mushrooms and he knows about, you know what liftoff means. And he was on the Joe Rogan podcast talking about how he was, you know, very anxious for some reason. And I think one of his trips had, you know, had fallen apart at the last minute, but he decided to do this beta system test anyway and under the guidance of a physician took pure bassist and and was waiting for the psychedelic experience that Paul Stamets probably knows better than anyone. Man, it didn't happen. But he felt an overall sense of complete calm and peace with the world. Interesting. And so, you know, that's where that makes sense in terms of serotonin to a activity. And it also, you know, n equals one but corroborates this collaborates with analysis doing I mean, the mouse isn't shaking its head. Paul Stamets isn't tripping. There's the cert powerful serotonergic effect and Paul's feeling calm.

Nick Jikomes 35:35

So remind me so base system is doing what at at the different receptors

Andrew Chadeayne 35:39

base system is doing nothing, because base system is a pro drug.

Nick Jikomes 35:42

Okay. Oh, I see. Okay, so that's the Northside lowson It turns into North silo so Yeah, exactly. Okay, so no, no psychedelic effect in this. N equals one Paul Stamets experiment, even though it's activating 5g to it, yes. Which we know from cellular acids. Interesting. Interesting. And so is it? Is it a mystery at that point? We don't really know what's going on there.

Andrew Chadeayne 36:05

Oh, well, I mean, we know more that's going on than ever now. Now. It's, you know, okay. Can we connect the dots even further? So okay, so we know, no HDR in mice, we know that it has certain serotonin to a activity. What else could be going on here? Wouldn't it be great to get that molecule into people? Because if it really is a show of fast acting, and zeolitic molecule that doesn't have really any, you know, toxicity issues or downside. That could be a good drug?

Nick Jikomes 36:38

Interesting. And are those studies underway? Are people doing them? We

Andrew Chadeayne 36:41

have some studies underway with North lowson and other North lowson. Pro drugs.

Nick Jikomes 36:47

Interesting. So as a before getting to that, as, as a chemist, and sort of at the level of pharmacology, how could it be that one drug activates 5g to a causes psychedelic effects? Another drug also activates the same receptor? And does not?

Andrew Chadeayne 37:04

What a great question. It's one of my favorite questions, and we're working on it. But, you know, working is the key there. And I think that's where we get into, there's got to be some sort of entourage effect, right? Like, it obviously isn't just banging on to a right because then anytime we push the to a button, we would get HTR. And people would trip. Right? So what else is going on there? There has to be some sort of, you know, I like the piano analogy, where it's like, you know, you're not just playing one note, but playing different notes, you start making chords, you know, call it the entourage effect, or whatever. But it's this sort of multifactorial, some of the pharmacology that creates the experience. And so, Nora solutions, a very dramatic example, because you basically turn off the property that you think it should have no matter what. But I think that to a lesser extent, those sorts of effects also explain you know, the, hey, this mushroom is more visual than this mushroom. This one has more of a body load, you know, you know, I'm more euphoric on this mushroom, so on and so forth. I think that's probably the spectrum of effects that are possible by modulating the pharmacology.

Nick Jikomes 38:11

Interesting. What about Mao is monoamine oxidase oxidase inhibitors have those been isolated from any philosophy species

Andrew Chadeayne 38:20

very, very recently, again, Dirk Hofmeister, who I think is probably the expert in magic mushroom biochemistry, his group has found a collection of beta carbon liens in magic mushrooms, and those are monoamine oxidase inhibitors. So these are the same things that are found in an Ayahuasca brew. I am not sure if it is the same monoamine oxidase inhibitor, I would guess that it's not, but it's the exact same idea that in ayahuasca, you have DMT, that gets chewed up by your body before it can do anything by monoamine oxidase. But if you co administer it, and I think it's like some sort of Syrian Root Bark that has it in the natural preparation, if you co administer the DMT with a monoamine oxidase inhibitor that shuts down the monoamine oxidase activity so that the DMT can go and do its thing. Yeah.

Nick Jikomes 39:10

And that's why DMT can be orally active if it's consumed with some of these inhibitors. Yes. And why is that interesting? Could that be the basis? Would you naturally think that's the basis for an entourage effect in mushrooms based on what else is inside these things?

Andrew Chadeayne 39:25

Yeah, I would be shocked if, okay, a lot of things going going on here. For one. There's really not that much of the beta carbon liens in Dirk Hofmeister his data. But again, these mushrooms are highly variable, like every way you look at them. So that's, that doesn't say anything about the batch of mushrooms that's, you know, growing on the coast of Oregon, you know, maybe they have a lot of beta Karpeles and beta carboline should affect the pharmacology considerably, at least insofar as monoamine oxidase is important in breaking down these molecules. Which brings up another question, right, like how important is monoamine oxidase in breaking down the molecules that you find in the magic mushrooms. Now, unlike DMT, all the tryptamines in the magic mushrooms have a force substitution with an oxygen atom can either be a hydroxyl group or a phosphate group. That group tends to inhibit monoamine oxidase from chewing up the molecule in the first place. So, looking at it that way, maybe the monoamine oxidase isn't that important, but you really don't know if the monoamine oxidase isn't affecting some other part of the breakdown of the molecule or the breakdown of some other molecule that is modulating the effects. So this all gets back to the overarching theme of, you know, look, you know, if you're going to look at a cocktail of molecules and ask what it does, you know, you're gonna have to account for all of those molecules in the cocktail, not just focus on one.

Nick Jikomes 40:52

And to what extent are you guys at Camtech? And in your research collaborations, are you working? Are you synthesizing these compounds de novo and working with pure preparations versus doing extracts that contain various combinations?

Andrew Chadeayne 41:06

We're doing both, I think Camtech sort of light bulb, or our contribution to this industry, you know, at least on the magic mushrooms side back in 2016 was, you know, look at the the whole composition. compositions are always molecules, right, we can't pick up a mushroom and call it psilocybin or say that it is just psilocybin. But then to my earlier point about how these cocktails with all of these molecules are really, really complicated. How can we possibly understand that, and so we're doing it very methodically, were start out with synthesizing and rigorously characterizing one of the molecules pure. And that alone is a step forward, because a lot of these molecules were either not available pure at all, or they were mischaracterized. A lot of folks tend to overlook different forms of the molecules, and different solvents or different salt forms of the molecules, which affects the molecular weight, which affects the, you know, all of the calculations based on molecular weight, which tends to be, you know, all of the biological considerations. So we start out by making pure versions of each of the molecules, then studying what the pure molecules do, and then moving on to how one molecule How would affect the pharmacology of another one. So take some medicine, right, the active from psilocybin, how does a little north close and affect that? It's got to be different? And then, you know, let's find something that we can quantify and then run with that. What does that do?

Nick Jikomes 42:38

And so in the psilocybin trials that are the most famous and publicized are those have those tended to be studies that have used pure psilocybin that they administer to patients, or are they using extracts that also contain at least small quantities of other compounds?

Andrew Chadeayne 42:56

I think, I always hate using the word all. But I think all of the clinical data is from pure psilocybin, I know that there are folks working on getting approval, you know, in Canada, and I think, you know, in some places in the US for using natural extracts or, you know, naturally sourced psilocybin, but I think still today, all of the human data for psilocybin is from pure synthetic psilocybin.

Nick Jikomes 43:27

Interesting. And have you guys done much work to characterize if there to a to try and like standardize cultivation so that the mushrooms growing harvest by harvests are relatively consistent? And have you done any work to rigorously characterize differences between philosophy mushroom species?

Andrew Chadeayne 43:46

No, to the first question, yes, to the second question. standardizing the chemo type of the mushrooms I know there are folks working on and it's just not us. You know, we have the one partnership where we're looking at biochemistry and actual mushrooms. And you know, what we're doing there is your second point, which is trying to get a rigorously analytical view as to what different sort of chemical fingerprints or chemo types there are across different species and really different samples of mushrooms. Because even for a given species, there tends to be a lot of variability.

Nick Jikomes 44:22

I see. So we mentioned DMT. briefly before in terms of the chemistry when we think about psilocybin, the active compound there that you metabolize is Siloso. And that's the one that actually causes the psychedelic effects. And then there's DMT. How do those differ in terms of the chemistry and how is it that such a small difference can lead to such a stark difference in the subjective effects?

Andrew Chadeayne 44:49

It's exactly what I was talking about before when we were talking about the monoamine oxidase inhibitors. So the difference between DMT and psilocybin So let's compare active to active the only difference there is an O H Per hydroxyl group and the four position of the tryptamine. But it's the inclusion of that, you know, oxygen atom there in the four position, that seems to lessen the ability of monoamine oxidase to break down the molecule.

Nick Jikomes 45:14

I see. So just that one tiny thing can have a big effect in terms of how it's how it's broken down.

Andrew Chadeayne 45:19

Absolutely, yeah. It lessens the ability of monoamine oxidase to break down the molecule. So you've got something orally active, that tends to sit around in the blood for four plus hours.

Nick Jikomes 45:29

And how does DMT compared to five Meo DMT?

Andrew Chadeayne 45:34

So five Meo DMT just has a five methoxy group added to the DMT molecule, if you want to think about it that way, using DMT as the base. And it seems as though I'm sure this is in the literature, that that substitution in the five position is not as effective as the substitution in the four position at inhibiting monoamine oxidase, which would explain why five Meo DMT is not orally active.

Nick Jikomes 46:01

I see. Interesting, interesting. And are you guys doing? Are you guys doing any work with DMT or five meal,

Andrew Chadeayne 46:06

not those molecules, specifically, we tend to stay away from the schedule on molecules. We use them as comparators. But everybody's working on those. But we've made a whole ton of analogs for each of those. So I mean, not five, not five, Mao DMT, but five, Mao with all sorts of different groups all over the place, and then compare it and see if we can figure out why the differences matter.

Nick Jikomes 46:28

Interesting. Is there anything interesting that you found with any of those so far that you can talk about?

Andrew Chadeayne 46:33

Sure. I mean, for one thing, like take DMT, or five, Ennio DMT. So the DMT stands for a Dimethyltryptamine. So on that ethanolamine arm, you have two methyl groups, if you start messing around with those methyl groups, you can make an orally active molecule. Why not entirely sure. Because I was just telling you before that, talking about sloths, and it's that substitution in the four position that shuts down monoamine oxidase. But you can also mess around with the the alkyl groups on the ethanolamine arm and change this non orally active molecule and do an orally active one.

Nick Jikomes 47:09

Does it appear to have the same sort of intensity and duration of effects? Or is that different as well?

Andrew Chadeayne 47:13

The problem is, is that right now we'd have to ask the mouse I see. So there you have as the head Twitch, well in there, and I hate to over interpret that data. Not in the five Meo DMT DMT space like I mean, we have created some versions of actually solution that look like they are blowing the mouse's mind compared to the standard, which would be like Cillessen, like, but what you're looking at is the number of times this mouse is shaking its head and like a 30 minute window, I see it more, a lot more. Or you know how little of the drug you have to give in order to get the mouse to reach the threshold of head shaking. But again, how much do you want to extrapolate? You know, the mouse is shaking its head with Right, right, right, curing this guy's PTSD? Yeah.

Nick Jikomes 48:01

Well, a question that springs to mind here that I realized that you're very uniquely positioned to talk about is you're creating and extracting and using some of these psychedelic analogues drug analogs of schedule one controlled substances. How does the legality come into this? When does you know, what's the legal situation? If something is not the schedule one drug but as a close analog and appears to have psychoactive effects? How does that like are those things legal? Do they easily become schedule one? How does all of that work?

Andrew Chadeayne 48:32

Great question. I actually, I mean, I think it's a little bit of a legal gray area. And I'll tell you sort of, you know, where we've drawn the line. So schedule one is pretty much outright prohibition for any reason whatsoever. If you have that molecule, we will assume that you are a bad person, and you're going to jail unless you have permission from the government. Right. And so we have a couple labs where we have that sort of permission for the schedule one molecules, these other not scheduled molecules, which I would call analogs, there is a federal analog act. Those are not scheduled one and not illegal for research purposes, right. However, if you were to buy them with the intent to eat them, or if you had the intent to distribute them, you know, if you got, you know, if you were in downtown Seattle, and you were on your way into a club and you had a gram of this research chemical on you, you don't really have plausible deniability that like oh, I was on my way to the lab. But we keep all of ours in a safe in a chemical lab, they all get delivered to the chemical receiving office and then cataloged and kept in a safe and one thing that we are very, very strict about at Camtech is like there's no eating the molecules like we are not Alexandra Shogun. I respect that guy's research tremendously. But you know, we got to color inside the lines here because we can't risk you know, some sort of disaster and we can do plenty of science, you know, playing by rules

Nick Jikomes 50:00

I see. So to summarize, the general rule is that if a novel analog is created, it's generally okay for research purposes, but not for other purposes. Yes, interesting. And you guys are doing I mean, you have sort of an interesting configuration at your startup, it seems you're very decentralized, are spread out, as I've learned chatting with you this morning. And you've had a lot of research collaborations with different universities, you're doing lots of different stuff. There's lots of different directions we can go can you just start talking about what some of the most interesting and intriguing collaborations you have are?

Andrew Chadeayne 50:34

Do you know, it's, that's like, you're asking me whether I like my son or my daughter better. You know, I could go kind of chronal I

Nick Jikomes 50:41

would love to, I love the I would love to talk about, you know, the area of psychedelics as addiction treatment. So I think you guys do have some collaborations in that area. So what's what's going on

Andrew Chadeayne 50:50

there? It's, that's our newest one. So and actually, might as well tell the story, because it'll give you an idea of Camtech. So our first research collaboration was with Professor David Mackay at UMass Dartmouth, we're doing a lot of synthesis and characterization, especially crystallography there because we ran into a problem in the industry that a lot of these tryptamine molecules are mischaracterized based on what crystalline form they occur occur in. Dave Mackay and I became friends at Peter wells and skis Lab, which was my PhD collect my PhD, where did my PhD work? Also in that lab, is Professor Elliot Holly, who is now at the University of Wyoming, who became another collaborator. He's a brilliant scientist, especially when it comes to kinetics. And so I was telling you about these pro drugs, we were looking at the relative hydrolysis rates of a whole bunch of different kinds of pro drugs to sort of get an understanding for how quickly we might expect these molecules to turn into the active. Elliot. Wonder if he wants me to tell this pass, probably okay. Elliot, in his lab at the University of Wyoming, inherited a bunch of cocaine in a safe from a previous professor and needed to get rid of the cocaine because he didn't want the cocaine in his lab, a new professor at the University of Wyoming Anna Clara Baba do, who studies addiction in animal models, wanted the cocaine for her research. And so after a whole bunch of dealing with the DEA, who just really was like, Why did you tell us about the cocaine? They were able to transfer the cocaine over to the scientist who wanted to use the cocaine for science, legal cocaine trafficking, right? But the lightbulb went on for Elliot in that, like, hang on, aren't these molecules that I'm working with supposed to treat addiction? Like, you know, AC, she goes by AC, you know, do you know, do you want to look into this, and he made the introduction and I couldn't be happier. I mean, AC is about as top notch a scientist as there is. And so we're working with her now. I think we've already once expanded the collaboration because she's that good at looking at whether our drugs can mitigate addiction in animals that have become addicted to a drug, how does an animal become addicted to a drug, you get, you know, a mouse or a rat hooked on cocaine or fentanyl. And you can look at this through a variety of different ways. One of them is placed preference, you know, you always give the animal fentanyl over here on this side of the cage that it understands is this side of the cage. And then later on, you know, when the animal is hooked on fentanyl, it tends to really like that side of the cage because it expects to get the fentanyl there. So two things we can do there one, does that happen with our drugs because we don't want to create a medicine to cure people that then they get hooked on. Right? So step one is like let's let's only use molecules that we're not going to create another problem. Step two is like now that we have these, you know, animals hooked on cocaine from Elliot, or fentanyl? Can we give them our drug and get them to seek out the bad drug and I think we all agree fentanyl is pretty bad, a little bit less. And so that's that's the work we're doing with addiction right now.

Nick Jikomes 54:00

Interesting. You know, one of the not just for addiction treatment, just with psychedelic therapies in general. You know, depending on your perspective, there are different views on you know, whether or not the actual psychedelic effects themselves are causally efficacious for the therapy, that they're actually part of the therapeutic process, or they're basically just an inconvenient side effect that makes you have to go through several hours of tripping and being supervised and all of that. So there's a big push right now to try and create non hallucinogenic, psychedelic drug analogs. Are you guys doing any of that? And do you have thoughts on the the plausibility of creating those types of compounds?

Andrew Chadeayne 54:41

Yes. Of all areas of what you said I'll just ramble for one. Yes. I think that there's, you know, a definite need for that. I don't think it's an either or at all. You know, there's the sort of debate is, is the psychedelic experience necessary? or the the therapeutic experience or for the therapeutic benefit. And I think that's just way too abstract or general, the example I like to use there is, you know, it might be necessary for you to work with your therapist through your trauma, you know, and you know, it might be necessary to gain some sort of profound new perspective on I don't know, a bad habit that you have, it's probably not necessary to treat your migraine, right, or, you know, some other sort of neuronal disease or something like that. So I think it's gonna be one of those sort of context dependent things. And my attitude towards that is like, why choose? Like, why can't we have both? We really, this is an exciting area, let's research all of it. So I love both sides of that argument, if you will, but I don't think it needs to be an argument at all.

Nick Jikomes 55:44

Right, right. Yeah. So your perspective is basically that there are probably certain things where the subjective effects are really important for the therapeutic effects. And there are probably other things where it's not. And for some people, depending on depending on what the ailment is, yep, you might want one, you might want the other.

Andrew Chadeayne 55:59

Yep. And I would ask, you know, this is another thing I always say like, I would ask the psychiatrists, like, that's not me, I don't know anything about treating people. I just know that we ought to know what the molecules are before we start testing them, or our data is not going to be very good.

Nick Jikomes 56:12

And have you guys created any? I mean, I know that other people have created analogs of hallucinogenic compounds that do not appear at least in animals to be hallucinogenic. Do you think we're gonna start seeing more of that? Are you guys doing any of that?

Andrew Chadeayne 56:25

I hope we're seeing more of that. Actually, I know, you're gonna see more that we just haven't published it yet. Yeah, we have a whole library of serotonin to a agonists that do not produce hedgewitch response. Whether they're useful or not, you know, I don't know. I know, David Olson is also working on some non psychedelic psychedelics, which is really cool, because I think, probably 10 years from now, we'll put all of this research together, and we'll have a pretty good idea as to the utility for those molecules, how they differ from the psychedelic ones. And, you know, keep in mind that that's sort of following a, what, 70 year hiatus on any research whatsoever? Yeah. And then this, the ones we're working on are largely based on Norse lowson, you know, normal, loosen the act of a bassist in which was this molecule that no one cared about or loved a few years ago at all. And, you know, to think that that could be sort of the launching point for a whole therapeutic class of drugs is also cool.

Nick Jikomes 57:20

What? Can you talk about Camtech? A little bit more. So it's, it's a super interesting company. I mean, you're obviously a private company. So you have to have a business model, but you're also doing a lot of this research, and you're publishing it, and at least some of it that goes out into, you know, public databases. So what's the structure of the company? And how have you thought about actually creating a sustainable, sustainable business out of this sort of love of this part of the research world?

Andrew Chadeayne 57:46

Yeah, really good question. I guess, I haven't really overthought it, you know, like I said, we we've focused on, like, the scientific problems. And so, you know, I tell my scientists all the time, never let me influence the science, you know, the commercials, I will handle the commercial side. And, you know, patents are sort of the answer to that. But let's just do good science. And part of good science is seeking the truth and not, you know, pursuing some sort of result that we want to have, which is why, you know, don't this isn't a bad result, like we may have, we might have just learned something. And, you know, business development is going to have to take one on the chin, but do the science. You know, like I said earlier, my initial career was a patent attorney. And I really, really geeked out over patenting natural products and new combinations and new versions of existing things. And so a lot of this fundamental research we're doing is, you know, supporting really great IP. And then with IP, you can go and ask investors for money that you can use to support science. And so that's the initial sort of launching point of Camtech is that by doing fundamental science, we can create fundamental IP. And then with the fundamental IP, we can, you know, get money to do more science

Nick Jikomes 59:11

interesting. So So in other words, as someone who came from academia, where, for those of you who have not been in academia, right, the PI, the principal investigator of a lab, is effectively the CEO of a small startup, and they're constantly trying to raise money, usually from the government. And right, because research is expensive. It's very technical, it's very labor intensive, it you know, it takes a lot of time and work. So you're basically saying you're creating an IP portfolio that will generate revenue that will allow you to actually do more research. And so you're sort of creating this loop in the private sector, where you can actually facilitate research that's going on in academia in many cases.

Andrew Chadeayne 59:48

That's the idea. I would encourage you to contact any any of our research collaborators and ask you what the easiest money they ever got was, and you know, the university is tell us the same thing. So hey, We really appreciate the work that you're doing seems like we share an area of interest. And, you know, we can pay for it, you know, and we can create IP, I mean, that's sort of my, you know, skill is bridging science and IP. And through that bridge, we can create value out of this, that we can go into the marketplace and get money to support the science and the world goes round.

Nick Jikomes 1:00:23

And so it sounds like in your role as CEO, scientists slash patent law guy, it's been really important to create a kind of separation of church and state between the business side of it, and the scientists doing the research.

Andrew Chadeayne 1:00:37

Not actually, I don't think there's really a separation, I think it's just kind of knowing the priorities, right? You know, you gotta I mean, science, I mean, science is sort of holy. You know, that's, that's the, you know, higher authority. But, sticking to that rule, there's still plenty of room for commercial interests, you know, these fundamental scientific discoveries, you know, although maybe not so obvious what the value is going to be, you know, right now, you know, they yield results and things that can be applied into new technologies that do have commercial value. And then using the patent system appropriately, you know, you can capture those applications and the technology that comes from the fundamental science later. And so I guess what we do is sort of trust the process and trust that it's going to work out, and we're going to find something, and we'll eventually be able to capitalize on it. Whereas I think, you know, some scientists or, you know, startup, you know, folks might run into the problem of like, well, I'm the investor, I need to know now where this is going. Whereas, you know, I think we now have enough of a track record showing that just trusting doing fundamental science, and that will get results that are valuable, does lead to results that are valuable.

Nick Jikomes 1:01:53

Can you give people maybe like a concrete example of something you've done? Or are in the process of doing in terms of like, when you when you create IP, and Camtech? What exactly is the IP? And what are its potential? applications?

Andrew Chadeayne 1:02:09

So, I mean, the IP would be any advance beyond the state of the art, right? So I mean, like, you know, go back to 2016, like, there was nothing here. And so, you know, really cracking any nut or solving any problems in advance, then the trick is like, Well, okay, how can I use this advance? How can I apply this into some sort of technology. So let's use the magic mushroom example, back, you know, in 2016 2017, there's no such thing as a standardized magic mushroom formulation. So figuring out how to make one, and then figuring out, you know, what those molecules are, and putting them together and explaining how to make these standardized formulations to, for example, create an entourage effect or, you know, change the pharmacology at some receptors. That was a big advance. Now, it was a gamble, a huge gamble, because think back then there's no psychedelics industry, there's no no decriminalization, no, Kevin Matthews in, in Colorado, no experts in Oregon, like, you know, by all, by all estimations, like, you know, this is just an interesting science project that is never going to have an application. But now, it looks like there might be standardized mushroom formulations out there, in which case, you know, we will probably have, you know, some avenue towards creating a product that's supported by IP.

Nick Jikomes 1:03:30

And when you say product there, so it's very natural, on the one hand to think about the, the medical and therapeutic side of this, obviously, if you're creating medicines, prescribed and used by doctors and therapists, you want them to be, you know, standard and reliable to have, you know, very particular formulations that you actually prove are good for one thing, or another. Do you guys think at all about or do your investors think at all about the commercial side? In terms of, you know, some of the stuff eventually becoming potentially consumer products do you does, is that a potential future that you see for psychedelics,

Andrew Chadeayne 1:04:03

I think we can contribute significantly to that area, I have no desire ever to make, like, or manufacture in mass produced products, I like more of the r&d side of it. And really, like, you know, when I started in that area, my only goal ever was, you know, if this ever happens, it'd be nice if the ingredients were on the package, right? It would be nice if, you know, not just psilocybin, but like these other molecules matter. So it's like, if I can affect this area in one way, it's that when this does happen, that on the package, it's just not like magic mushrooms, psilocybin content. 1%. Yep. Somebody has paid attention to these other molecules, you know, because they, you know, probably matter.

Nick Jikomes 1:04:46

Yeah, I mean, that's still to this day, a big issue in cannabis where like, the majority of packaging, it just sort of says THC, CBD, and you don't get a lot of information about the other stuff. And in many cases, the consumer doesn't even know there's no awareness that they're even Is other stuff that might be there? Yes.

Andrew Chadeayne 1:05:03

Although, you know, I think the positive spin on that is that it's changing very fast in the right direction, I think in that, you know, pre Eboo no one ever even mentioned the name of those molecules and then yeah, you're right like now you can see THC THCA CBD CBD a on the back of some of the products. I was in a dispensary down by climate pledge arena. The other day the I forget the name of it. And I went in there and there was because I was like to see what's going on with the products. There was a mint that you could buy that was like, CBD, CBC and CBG, no THC, you just take it, I guess, with your cannabis to balance out the THC effects. And I was like, wow, like, you know, there's at least two molecules that nobody knew existed five or six years ago?

Nick Jikomes 1:05:57

Yeah, no, we are seeing more and more of that. So it'll be interesting to see where it goes. What kind of what kind of investors has cam tech attracted? So you have this sort of model where you've basically sold the idea that we're going to create this big IP portfolio, and we're basically just doing basic research and r&d stuff to do that. From from what sectors? Have you gotten interest? Is it mostly people that are that have an eye for developing pharmaceuticals and therapeutics? Or or is there more to it than that?

Andrew Chadeayne 1:06:31

Probably an unsatisfying answer. Are initial seed round investors were people who saw opportunities to make, you know, big returns on investment? You know, uh, well, you know, that's, I mean, I think when we did our seed round, right, there was no indication of any decriminalization or legalization period, right. So like, throw all that away, and you had compass pathways over there, like, you know, maybe developing psilocybin and maps a nonprofit, was developing MDMA, which you could argue is or is not a psychedelic? You know, and I think that the investors saw that we were, you know, you know, really, really early, and that we had the skills, you know, that were good to have really, really early. And so that's probably how we, you know, you know, we're fortunate enough to get in touch with that group of investors. And then our series, a round was led by the noetic Fund, which is a fund that is largely focused on psychedelics as sort of a specialty industry group.

Nick Jikomes 1:07:31

Interesting. So what other kinds of research collaborations Do you have, like areas that we haven't touched on yet? Is there any, are there any major ones that we haven't gotten

Andrew Chadeayne 1:07:38

to NIH, and the National Institute of Drug Abuse? I think we were the first sort of industry and because again, we were the only ones there for a while doing science. But I think we were the first to collaborate with the government, really, I mean, the NIH NIDA, in studying these molecules, they're very interested in it, which is sort of how we find our collaborations. It's like, oh, you know, you like studying this. I like studying this. Let's study this together. And then we'll kind of make it work out in the agreement. And so we have a collaboration with NIH, Nida. That's where we do our telemetry. So I mean, we can measure temperature, depression, hedgewitch response locomotor activity, after giving the animals drugs. We're working with some very talented scientists there on that. And then through that collaboration, we have access to the PDS P database. And that's Brian Roth's project. And that's where we can do some binding affinity assays. And then, you know, you take a step back and look at all that sort of, from a 10,000 foot view, you know, we've got Dirk Hoffmeister over here, where we're trying to figure out what the mushrooms are making and why. And then take that all the way through to, you know, preclinical models for you know, addiction, and also, you know, some other diseases and conditions. And then this year, we added a CSO who's a farm of that. And we're doing formal preclinical testing, moving into clinical trials for a bunch of stuff. So it's, it's taken a while to come together, it's come together all very organically, but it's really sort of a mushroom to human clinical trial machine at this point.

Nick Jikomes 1:09:24

And are you mainly focused on psychedelics that are related to the contents of magic mushrooms or four, do you work on other stuff at a significant level?

Andrew Chadeayne 1:09:36

I would say tryptamines would be my favorite. You know, and yeah, that's magic mushroom inspired right? Yeah, then like, like I say, pull away the hydroxyl group. And

Nick Jikomes 1:09:45

it's like, to me, I'm

Andrew Chadeayne 1:09:46

working with DMT analogs and add a five methoxy group and I'm working with Toad compounds. We have a couple of outliers in there that we're looking at the molecules and m&e to Muscarella.

Nick Jikomes 1:09:58

Interesting, and those are more like Uh, they're they're not tryptamines they're not tryptamines. Right? Can you describe what those are for people because that's an interesting difference, I

Andrew Chadeayne 1:10:05

think, um, you know, early in the research, it's a ibotenic acid, but totally different structures, and it totally different mushroom like, this is the really cool looking red mushroom with the white spots that's in Super Mario Brothers. And the effects are, I think very poorly teased out as well. I've read a bit about it. I actually have never spoken to anyone who's taken Amanita muscaria mushrooms, but like the stories that I've read is like, you know, people will kind of come out of their trip like 10 miles from home having thought that they were a deer, and then have cuts all over themselves, because Geez, how did I get over those barbed wire fences? Well, I thought I was a deer. You know, so I'm not. And it works on totally different receptors, right?

Nick Jikomes 1:10:53

Yeah. So like Musa Maul, which comes from hypothetic acid, I believe these are basically like sedative hypnotics almost like a benzodiazepine. So yeah, it's just very, very different chemistry going on there

Andrew Chadeayne 1:11:04

yet. But when I say early in the process, right, like, what else is in that matter? And so the farthest along is probably magic mushrooms and magic mushroom analogues. But I mean, you know, early on in the earlier stage would be, you know, Amanita muscaria. Or here's another one for you. What are all those other molecules in Toad secretions?

Nick Jikomes 1:11:25

You've got it's gotta be a lot.

Andrew Chadeayne 1:11:26

You've got the Save the toad people out there who I support, right? Like, please don't kill the Bufo out there as Toad. It's a nice toad. But then you've got these other people who say that synthetic five Meo DMT is just nothing like the real stuff. And then so I mean, and that's right up my alley, right? That's a will. Okay, so there's a difference? What is the difference? I bet it's a chemical. Like I bet if we look at the chemical composition, we're gonna figure out why there's a difference. And then, you know, where I think that work could be important is that if we can closely enough mimic the toad secretion, then maybe we don't have to go and mess with the totes. Right? Right. But like, right now, it seems like there's at least, you know, a camp out there that says that the five Meo DMT is just, you know, not the same as the toad secretion. So there is no substitute. I'm not going to take a caffeine pill in the morning, I need my coffee.

Nick Jikomes 1:12:17

Yeah, no, that's, that's the basic idea. So you've got I mean, you've sort of found a very interesting niche for yourself. And you said, a couple of things I want to go back to, I think, you know, there are probably a solid number of PhD students and postdocs that listen to this podcast, that are thinking about, you know, other things as as many people do when they get to that stage of their career in academia. You said a couple things that were really interesting to me at one point, you said, you know, I've tried not to overthink it. And then you, you mentioned that right, you were a chemist, but then you decided you wanted to go into patent law, and you created this kind of superpower by having these two sort of domains of expertise. Yeah. Can you talk a little bit about the psychology there, and the not overthinking it, and sort of how you've created a niche for yourself by sort of, by by creating expertise in two different, like, separate domains?

Andrew Chadeayne 1:13:07

Sure. A, I think that that is, that is how you get a superpower. And then the other lesson here is, you know, listen to your wife or partner. Because it's not easy at the time. I mean, I was a struggling chemistry graduate student, and my PhD advisor described me as a typical b minus student. That's, that's Andy is your typical b minus student. That's a quote that everyone in the group likes to remind him of these days. You know, but, you know, being a, well, first of all, being a typical b minus student in people's Ancel Keys group is an achievement, I think. But then second of all, like, as soon as you take your typical b minus student out of this very, very high level program, and put that person anywhere where that skill can be applied, there's the superpower, right? Like, you know, I could have gone into actually did dabble in brewing, right? There's a nice chemical application, natural products and drugs would be another one, like, I bet I, you know, have a whole career ahead of me and the coffee industry or you know, something else, like something where you have a natural passion or interest in it, and some way to apply, you know, the earlier skill. And that was patent law. For me initially, it's like, oh, well, I guess I'll never make it as a chemist. But over here in this law firm, like, oh, you know, people appreciate me for my for my chemistry. And now it's actually probably three things, you know, the sort of earliest interest which was like drugs and pharmacology, then learning chemistry, and then, you know, sort of outside this podcast, but developing expertise in chemical patent law has also been very helpful. And then sort of sort of combining those three things together. You know, anyway, to support your hypothesis, like having the As to skills, the combination, I think you can do something way cooler than just having one skill.

Nick Jikomes 1:15:05

And, you know, the part about not overthinking it, that's, that's something I've learned over the years as well. What Why do you think that's important?

Andrew Chadeayne 1:15:15

You know, maybe that wasn't even the best way to say it. Like, really in this, this gets back to, you know, listen to your, your, your partner, my wife has always been very supportive in me of, you know, don't worry about the money, don't worry about, you know, the reputation or the career success or whatever, like, you know, focus a little bit more on, you know, what you like doing. I've also in the past, worked with a really good friend and executive coach, Miranda holder, she runs an executive coaching firm. And, you know, she would always encourage me to follow my gut, you know, what's your gut telling you? Well, you know, not not what you have to do or what you should do. But what do you want to do today? And I think that that's very hard to do, especially as you get more and more responsibility and more investors to answer to, to, you know, not do what everybody thinks you should do. But to go and you know, we used to use the term, follow your nose, and do something you think's interesting. But I swear that nine times out of 10, it is that sort of freedom to go and follow my nose, or go and do give myself permission to do the thing that's interesting. That causes me to bump into something that has a relationship to the thing that I should be doing. And then all of a sudden, like, genius, like, Oh, how did you ever make that connection? It's like, I don't know, I was walking around in the yard.

Nick Jikomes 1:16:38

How do you approach managing this company? Because you've got all these academic research collaborations, you've got the legal side of it, you've got investors to answer to, you know, I imagine you probably don't have a typical day, but how do you how do you balance and juggle all of these different complexities that that are involved here?

Andrew Chadeayne 1:16:56

I mean, hopefully not poorly. Yeah. I don't know.

Nick Jikomes 1:17:01

It's just another case where it's important not to overthink it.

Andrew Chadeayne 1:17:04

No, here, I think the really important thing is, have great people around you. I'm probably a terrible manager, you know, probably terrible at ops, or finance. But I have excellent people that are working with me at Camtech. You know, one of the compliments that I've gotten in the past, you know, several times is that I'm good at sort of staying in my lane. You know, as CEO, that's very hard, because the whole darn thing is my lane, right. But at the same time, like, I try to make sure that I'm working with people that you know, have a given expertise, and that they are confident in their expertise, and then I try to defer to them and empower them in their area to really own that area. You know, I don't question my finance guy about finance. I mean, I might ask for something to be explained. But, you know, I think that's how I've gotten through, it's, it's not me, it's just that I have a lot of, you know, really talented and good friends and colleagues have developed, you know, over the years,

Nick Jikomes 1:18:06

how do you actually find good people like that, and I mean, that in the sense of, like, I'm guessing, and maybe I'm wrong, I'm guessing that not everyone in your company that reports to you is as deeply passionate about chemistry and psychedelics, as you were? And so what attracts the good people? Or am I wrong about that?

Andrew Chadeayne 1:18:26

I don't think it's a right or wrong thing. I think it's, um, you know, a line drawing problem. And that's one thing that I try to do in every relationship, that every new relationship at Camtech is, you know, what are you interested in? And what do you want to do? And, you know, what, what would you enjoy working on? And also, what don't you want to do? Because if we can make if we can find or create a role for you doing what you want to do, you're probably going to like that. And, you know, I think the only way to do great work is to, you know, love what you're doing. And so, you know, take every one of the scientific collaborations, right? Like, I didn't go in there and say, Okay, I'm going to give you money. And I expect you to give me these deliverables. And you can do your own science on your own time, and I don't want to hear about it. It's more of a wow, I really love the science that you're doing. And, you know, do you think that you might want to do some of that with my molecules? And then oftentimes, the answer is like, wow, I'd love to have access to your molecules look great. Let's do it. And now, I don't need to manage you.

Nick Jikomes 1:19:29

Yeah. Interesting. So a question that that I often ask people is, and, you know, you've probably partially answered this already, but it's okay to reiterate if if we need to, what are some exciting, outstanding questions in psychedelic science? That we don't know the answer to today, but that you think we'll know the answers to relatively soon 234 years from now?

Andrew Chadeayne 1:19:54

That's tough because some of them are like, you know, things that I want to know the answers to 234 years from now. I think the entourage effect is one. And I think that's well within our grasp, at least in the two, three molecule pairings. That'll be interesting to kind of, at least have, you know, a good working understanding and some predictability about the different effects of different magic mushrooms based on their chemical composition. Another one that fascinates me and I know this fascinates Paul Stamets and some others now to it's gaining additional attention is would love or paralysis, there is a phenomenon out there where certain magic mushrooms highly, highly correlated with magic mushrooms that grow on hardwood substrates. So like your Salafi sign essence, your philosophy as the resins and related species and other parts of the world, people will eat these mushrooms and they will have your typical magic mushroom trip, I can't believe I just said typical magic magic mushroom trip. But then, you know, later on, you know, hours after the trip or even into the next day, throughout the next day, these people will have muscle paralysis. We've done a lot of survey work on this and you know, talking to a lot of folks, but it's sort of like your muscles get fatigued. Really, really easily and really powerfully. So it's like, you know, one of the best examples would be like, you know, you get up in the morning and you start buttoning your shirt. And by sort of the third button, you can't button the fourth button. What is going on scary stuff. So we're collaborating with. She's like 20 people on this now, everything from Dirk Hoffmeister, and like, hey, and what's the difference in these mushrooms? Because again, it must be a chemical difference, you know, different effects, there's got to be a different it's a different drug. It's not psilocybin, it's something else is going on. So what's in these different mushrooms? And can we correlate some sort of chemical difference with a higher incidence of the wood lover paralysis? You know, and is that a species or genetic thing? Or is this like a patch by patch sort of thing that like, we don't know yet. I mean, for all I know, it's like mushrooms that grow on Alder that were next to a rhododendron plant. I mean, that's possible. But figuring that one out, I think it's going to be really important. And it's also been one of our really fun projects, because it's purely a puzzle. And it's a puzzle that fascinates the pharmacologists and the biologists alike. But I say that that's going to be of increasing importance because everybody is running around right now to decriminalize or call off the dogs on on magic mushrooms, which I think is going to give rise to kind of craft magic mushroom industry because boy, don't I want the most potent one. I heard that one. So cool. And then what's going to happen? People are going to show up, you know, at my wife's work, she's an ER doc, with late onset paralysis that sort of looks like a disease called myasthenia gravis. It also looks like, you know, something that might shut down like airways and stuff like that. So people could wind up in the hospital getting intubated. Which could dramatically frustrate some of these, Hey, call off the war on magic mushrooms movements. So

Nick Jikomes 1:23:15

interesting. Yeah. No, that's, that's interesting to think about. What's Um, well, I mean, what are some of your favorite ongoing projects that Camtech that we haven't touched on? Is there anything in particular? Oh, man. I mean, it sounds like you're doing an incredible diversity of things.

Andrew Chadeayne 1:23:30

I we're all over the place. All because and one of my co founders, Davis wooley uses, you'll taught me this analogy. And I think, to a large extent, it was true, at least early on. I don't know if you've ever been to like a fourth of July pool party, where they throw a lot of coins and stuff down at the bottom and then say go and you know, you go down there and try to pick up as many coins as you can. Like, I feel like that was the early days of Camtech. It's like, wow, like, you know, nobody knows anything around here. Like there's all these cool things to go and do. And we could be first we could be first over here and here. And so that's where a lot of the diversity came from. You know, there were just so many places to move into. To your question about, you know, other stuff that like, I think it's really cool right now. We've been, I think I mentioned earlier, some of these molecules have been, you know, mischaracterized forever in the literature. And then, you know, when I say Miss characterized, you know, you might call Well, I mean, this actually just happened to compass pathways, right? They were referring to psilocybin, as, you know, their psilocybin Form A, or whatever they were calling it, but it was really a hydrate, right? A big deal, right? There's just some water in there. Well, you know, that's 18 grams per mole of a difference. And that seems to be an issue that is just ubiquitous throughout this class of molecules and that you can have different salt forms you can have, you know, two tryptamines per era. In ion, so a dye and ionic two tryptamine thing, you know, there's the Freebase molecules, you can have 1234 plus molecules of solvent included in in all of these instances, you know, the, the molecular weight of the molecule is wrong. Which means that, you know, when our biological collaborators go to very carefully weigh out milligram quantities of this molecule, that everything looks great. They're, they're weighing out a molecule that they have the wrong identity of. And so when they go to use the molecular weight to calculate how many moles they used, or what the potency is, all the way down the line, you know, all the numbers are wrong. And so that was something that frustrated me a lot early on, and that you look at the literature and you look at the data there, and you're I don't understand why our numbers are a little bit off. And it's like a Ha, it's because all of these numbers are wrong, because all these molecules are mischaracterized. And so we're trying to come up with some, I mean, first of all, characterize all the molecules, and then also come up with some ways to quickly measure the differences and avoid mistakes. And, you know, figure out ways to guarantee one form over another form, basically, so that, you know, all of the scientific data can build upon a good foundation instead of a shaky foundation.

Nick Jikomes 1:26:20

And if people want to keep abreast of the research that you're doing, or that's adjacent to what you're doing, is there a place like your, like a website or social media that you have that you can point people to? And also, can you maybe just sort of give a list of some of your collaborators, again, that people might look up and follow on, you know, Google Scholar or something like that?

Andrew Chadeayne 1:26:40

Yes. So for one, we do look to your earlier point, we do try to publish, you know, I think it's our responsibility of scientists to, you know, publish our results. And that's something that we honor with all of our collaborators, because they're scientists. And so the academic literature is probably the best place to learn what we're doing, and we try to get it out there. You know, as soon as we, you know, dot our i's and cross our T's with IP, try to get the information out there so others can use it. Then we often post updates on our webpage, which is cam dot tech, ca m.te. Ch. Social media, I think we have a Twitter, I sometimes post on LinkedIn, but we are not very loud on the sort of self promotion side. We do try to be good and do our job and in the scientific literature, but I'm not sure if we actually I don't think we've ever paid for a promotion, or

Nick Jikomes 1:27:37

you post anything that you publish on your website.

Andrew Chadeayne 1:27:41

No, not everything, but some some select things. But everything that you know, well, scientific literature is probably the most comprehensive place that we would publish this stuff.

Nick Jikomes 1:27:52

And just in terms of like, just the general area of magic mushroom chemistry, let's say. Can you say again, some of the top names there if people want to go dig into that literature?

Andrew Chadeayne 1:28:02

I mean, I think Dirk Hoffmeister is the number one guy in magic mushroom biochemistry. You know, I'm biased, right? I mean, he's my collaborator. And I'd call him a friend now. And his group, but I mean, he seems to be pushing the envelope forward at all of these sort of fundamental questions that we're talking about, you know, finding new molecules and mushrooms, understanding the underlying biochemical processes for how they get made, so on and so forth. So that would be, you know, on the, on the biochemistry said, you know, my first stop on the sort of magic mushrooms side. It's hard to tell, because, you know, a lot less than the scientific literature there and a lot more, kind of press release. See, I don't know if this is peer reviewed sort of data. I tend to think the stuff I see from Alan Rockefeller is really good. He seems to be a really good mycologist Paul Stamets is, you know, I think the, you know, godfather of the whole magic mushroom area. And then, you know, I think it's also important to look at sort of different sources. I mean, Paul Stamets is a mycologist. And so that's sort of that group that, you know, you know, since Geez, he's been in it forever, but focusing on the mushroom, right? Not the molecules, right. And that's where, you know, looking at Paul Stamets is understanding of certain magic mushrooms and you know, how they might affect people. And then also looking at what Dirk Hofmeister is doing to try to get clues as to what's going on over there. Those two things are important. And then the folks that you Sona on the synthetic side have done a lot of really nice work. I really like you know, the work from Alexander Sherwood. In his group they've they synthesize Bay, Asst and a Rogosin, and Norse lowson and had a nice paper on that a few years. years ago. So that's coming up the magic mushrooms from the more synthetic side. And they also along with Adam Halberstadt did some good animal behavioral assays with those molecules.

Nick Jikomes 1:30:15

Well, Andrew, this has been, this has been fascinating. I definitely learned quite a bit that I didn't know before. Is there anything any final thoughts you have that you want to leave people with? You know, just in terms of what we talked about, or anyone who's just generally interested in this area of the scientific, the scientific universe.

Andrew Chadeayne 1:30:33

I wouldn't know where to begin with a final thought. I mean, we could go on for hours that have no not really I think we've hit you know, some some really exciting areas and I thank you for having me on the podcast.

Transcribed by https://otter.ai

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